Wang Hao, Mengsteab Senait, Tag Carmen-G, Gao Chun-Fang, Hellerbrand Claus, Lammert Frank, Gressner Axel-M, Weiskirchen Ralf
Department of Laboratory Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China.
World J Gastroenterol. 2005 Apr 7;11(13):1929-36. doi: 10.3748/wjg.v11.i13.1929.
Considerable attention is focused on polymorphisms in the gene encoding transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine that is in turn a potent growth inhibitor involved in wound healing and differentiation. In humans, it promotes the pathogenesis of organ fibrosis, atherosclerosis, cancer, autoimmune and inflammatory diseases, keloid disease, and hypertrophic scarring. For this reason, much emphasis has been placed on studies elucidating the impact of TGF-beta1 and its gene variations for the susceptibility and pathogenesis of these diseases. Unfortunately, some studies have serious limitations.
We have recently described a high-throughput method for investigation the Arg25Pro polymorphism of human TGF-beta1 gene and showed that the frequency of the Pro25 allele is significantly associated with hepatic fibrogenesis. In this report, we describe two novel LightCycler (LC) techniques that facilitate the examination of the two other known alterations in the coding region of TGF-beta1. We investigated whether these polymorphisms contribute to hepatitis-induced progression of fibrogenesis in Chinese and Caucasians.
In the Chinese ancestry, the gene polymorphisms at codons 25 and 263 were not found and the genetic variant at codon 10 is unlikely to confer susceptibility to hepatic fibrosis. Contrarily, in Caucasians TGF-beta1 allelic variations are more frequent and the presence of prolines either in codon 25 or 10 is associated with the interindividual variability in developing more severe fibrosis during chronic hepatitis C infection.
In summary, these results confirm the hypothesis that TGF-beta1 polymorphisms are associated with fibrosis progression in Caucasians chronically infected with hepatitis C.
转化生长因子-β1（TGF-β1）是一种多功能细胞因子，又是参与伤口愈合和分化的强效生长抑制剂，编码该因子的基因中的多态性受到了广泛关注。在人类中，它促进器官纤维化、动脉粥样硬化、癌症、自身免疫和炎症性疾病、瘢痕疙瘩病和肥厚性瘢痕的发病机制。因此，人们非常重视阐明TGF-β1及其基因变异对这些疾病易感性和发病机制影响的研究。不幸的是，一些研究存在严重局限性。
我们最近描述了一种用于研究人类TGF-β1基因Arg25Pro多态性的高通量方法，并表明Pro25等位基因的频率与肝纤维化显著相关。在本报告中，我们描述了两种新颖的LightCycler（LC）技术，它们有助于检测TGF-β1编码区的另外两种已知改变。我们研究了这些多态性是否促成中国人和高加索人中肝炎诱导的纤维化进展。
在华裔人群中，未发现第25和263密码子处的基因多态性，第10密码子处的基因变异不太可能导致肝纤维化易感性。相反，在高加索人中，TGF-β1等位基因变异更为常见，第25或10密码子处存在脯氨酸与慢性丙型肝炎感染期间发生更严重纤维化的个体间差异有关。
总之，这些结果证实了TGF-β1多态性与慢性丙型肝炎感染的高加索人纤维化进展相关的假设。
